Injectable polypeptide-engineered hydrogel depot for amplifying the anti-tumor immune effect induced by chemo-photothermal therapy

摘要

The immunosuppressive tumor microenvironment has caused great obstacles to tumor immunotherapy, especially where less tumor-associated antigens are released from tumor sites. Herein, a Ag2S QD/DOX/Bestatin@PC(10)ARGD genetically engineered polypeptide hydrogel PC(10)ARGD as a sustained-release material was developed for mammary carcinoma treatment. A near-infrared silver sulfide (Ag2S) QD as a photosensitizer was encapsulated into the hydrophobic cavity formed by the self-assembly of the polypeptide nanogel (PC(10)ARGD) for photothermal therapy. The water-soluble drug DOX and Bestatin were integrated into the PC(10)ARGD hydrogel. The photothermal effect could trigger the sustained release of the DOX, which could be applied to initiatein situvaccination. Bestatin as an immune-adjuvant drug could amplify the body's immune function. The results ofin vivotherapy tests exhibited that the Ag2S QD/DOX/Bestatin@PC(10)ARGD hydrogel with laser irradiation could activate anti-tumor immune effects that inhibit the growth of primary tumors and distal lung metastatic nodules. Meanwhile, a safer lower-temperature with multiple laser irradiation treatment strategy exhibited more effective tumor-killing performance (84.4% tumor inhibition rate) and promoted the penetration of immune cells into the tumor tissue. The CD8(+)and CD4(+)cytotoxic T cells ratio was increased by 5.3 and 10 times, respectively, thus exhibiting a good prognostic signal. The multifunctional polypeptide hydrogel as a green manufacturing and engineering material is promising to serve as a cancer vaccine for anticancer applications.